Brown neuroscientists who taught rats a new skill found that not only had the
animals’ behavior changed but so had their brains. The research appears in
the current Science.

PROVIDENCE, R.I. — A new study by brain scientists at Brown University
provides evidence that learning engages a brain process called long-term
potentiation (LTP), which in turn strengthens synapses in the cerebral cortex.

The study provides the strongest evidence to date to support the 25-year-old
hypothesis, generally accepted by neuroscientists, that learning uses LTP to
produce changes in the connections (synapses) between brain cells (neurons) that
are necessary to acquire and store new information, said lead author
Mengia-Seraina Rioult-Pedotti.

Neuroscientists also theorize that higher forms of learning occur in the
cerebral cortex. Evidence from the study supports that theory.

In the study, published in the Oct. 20 issue of Science, Brown
University researchers taught rats to reach into a hole in a box to grasp food
pellets, a new motor skill for the animals. After five days, the rats were
tested.

The researchers found that not only had the animals’ behavior changed,
through the learning of a new skill, but that their brains had also changed.
Associated with that learning, the strength of synaptic connections between
neurons in the motor cortex had increased through a process consistent with the
use of LTP.

“Importantly, the overall range of synaptic modification – the
maximum possible increase or decrease in strength – had not
changed,” said Rioult-Pedotti, a neuroscience investigator. “Using
this synaptic modification range as a reference allowed our group to eliminate a
weakness of earlier work,” she said.

In previous studies, the researchers showed that synapses were modifiable
through the LTP process when those synapses were activated artificially by
electrical impulses. “However, it was not known whether LTP was actually
used to modify synapses when learning takes place in the living brain,”
Rioult-Pedotti said.

“The link between LTP, synaptic modification and learning was
tentative,” said senior author John Donoghue, professor of neuroscience.
“This latest study provides strong evidence that learning itself engages
LTP in the cerebral cortex as a way to strengthen synaptic
connections.”

The research also provides a model to study the relationship between learning
and synaptic activity. For example, “the model may be used to study
whether synaptic connections get stronger or weaker when you continue learning
for long periods of time,” Donoghue said. “Or, it gives us a model
to test whether drugs or other therapeutic agents can be used to enhance LTP or
learning.”

Learning and memory are thought to occur through LTP. This is a system in
which synapses become increasingly sensitive so that a steady level of
pre-synaptic stimulation becomes converted into a larger post-synaptic output.
LTP involves patterns of synaptic strengthening and weakening that can last for
weeks.

The research further validates the assumptions of a theory proposed by other
Brown researchers which says synapses are constantly modifying and that the LTP
process is closely related to learning, said Rioult-Pedotti.

Rioult-Pedotti and Donoghue are continuing to examine the relationship
between learning and LTP. In particular they are studying which cells and genes
are involved in the learning process.

The researchers are also looking at the effect of different training programs
on synaptic changes. “We’d like to find what kind of training
programs initiate or sustain changes in the cortical circuitry,” Donoghue
said. “Is there a brain basis for different kinds of learning? How could
you learn something optimally?”

Former Brown undergraduate Daniel Friedman was also an author for the
study.